Citations

ABSTRACT Newly diagnosed patients with non‐Hodgkin lymphoma (NHL) often have a history of other diseases, and these comorbidities can impact patient treatment and management options, as well as overall survival (OS). We developed the Lymphoma Epidemiology of Outcomes (LEO) comorbidity index (LCI) as a sum of 10 comorbidities adapted from the Self‐Report‐Generated Charlson Comorbidity Index (SRG‐CCI) for use in the LEO cohort, a national prospective study of newly diagnosed NHL. Of the 5502 participants with self‐reported comorbidity data, 3107 (56.4%) were male and the mean age at diagnosis was 60.9 years (range, 18–99 years). The LCI ranged from 0 to 6, with 48.6% having 0, 30.2% having 1, 21.2% having 2 or more comorbidities. With a median follow‐up of 62.4 months among surviving participants, 2099 patients had an event and 1219 died. Continuous LCI similarly predicted both 1‐year mortality (c‐statistic = 0.654) and OS (c‐statistic = 0.655), while it showed a weaker but still statistically significant predictive ability for lymphoma‐specific (c‐statistics = 0.617) and event‐free (c‐statistic = 0.574) survival. Participants with 1 (HR = 1.21, 95% CI 1.05–1.39) and 2+ (HR = 1.80, 95% CI 1.56–2.08) comorbidities had inferior OS compared to those with no comorbidities after adjustment for age and sex (c‐statistic = 0.654), and performance strengthened after adjustment for the International Prognostic Index (c‐statistic = 0.672). LCI predicted OS most strongly in marginal zone (c‐statistics = 0.748) and weakest in T‐cell (c‐statistic = 0.579) lymphoma. The cumulative incidence of death due to lymphoma, lymphoma treatment, and other causes all increased with increasing comorbidities, with the greatest increase observed for death due to other causes. The LCI performs comparable to other published comorbidity indices, supporting its use in the LEO cohort to better model real‐world outcomes and more generally providing an approach to implementing comorbidity indices in cancer survivorship cohorts.

Purpose of review Sulfate is essential for the sulfation of proteoglycans to maintain cell function. The mechanisms regulating the ‘ins and outs’ of systemic sulfate balance remain incompletely understood. SLC26A1 is an anion exchanger expressed in the kidney. It has recently been identified as a key regulator of plasma sulfate homeostasis in humans. This review summarizes current insights into SLC26A1 function and its role in human diseases. Recent findings Slc26a1-knockout mouse models exhibit reduced plasma sulfate and abnormal sulfate and oxalate homeostasis, accompanied by augmented susceptibility to acetaminophen-induced liver injury and kidney stone disease, although findings on oxalate homeostasis are inconsistent. In humans, rare and common SLC26A1 variants are associated with hyposulfatemia, musculoskeletal abnormalities, and, in some cases, nephrolithiasis. Functional assays confirm disrupted sulfate and oxalate transport of damaging variants. However, the knockout mouse models have been incompletely characterized, and few patients with damaging SLC26A1 variants have been characterized regarding sulfate and oxalate homeostasis and associated diseases. Summary SLC26A1 emerges as a key regulator of sulfate homeostasis, with potential roles in hepatic detoxification, skeletal integrity, and kidney stone disease. Additional mouse models with tissue-specific gene deletion are needed to delineate the role of SLC26A1 in sulfate and oxalate homeostasis as well as disease pathogenesis. Identification of additional patients with damaging variants in SLC26A1 as well as larger population studies may help to elucidate causal relationships of SLC26A1 activity with clinical outcomes.

Background: Coronary artery disease (CAD) is common among liver transplantation (LT) candidates, yet whether pre-transplant percutaneous coronary intervention (PCI) improves post-LT outcomes remains uncertain. Methods: We conducted a single-center, Institutional Review Board-approved cohort study of adults undergoing LT from 2005 to 2025. Asymptomatic candidates with significant stenosis on invasive angiography were included; prior coronary artery bypass grafting was excluded. The primary endpoint was major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke/transient ischemic attack, new systolic dysfunction, post-LT coronary revascularization, or all-cause death). Results: Among 111 patients (median age 65 years; 84% male), 66 (59%) underwent PCI and 45 (41%) were managed medically. Over a median 32 months of follow-up, 61 patients (55%) experienced MACE. Composite MACE did not differ between PCI and non-PCI groups (52% vs. 60%, p = 0.40; log-rank p = 0.59). Fine–Gray modeling showed no association of PCI with MACE; independent predictors were prior MI (HR 1.81, 95% CI 1.01–3.24) and pre-transplant dialysis (HR 2.13, 95% CI 1.07–4.24). Major bleeding occurred in 7%. Matched and era-stratified analyses were concordant. Conclusions: In asymptomatic LT candidates with angiographically severe CAD, pre-LT PCI was not associated with a lower incidence of post-LT MACE.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

ABSTRACT Introduction Sinonasal sarcomas are exceedingly rare entities, constituting less than 7% of head and neck sarcomas. Their complex histology needs specialized treatment, which is often based on multimodal approaches including surgery, radiation therapy, and/or chemotherapy. This manuscript aims to gather expert opinions to establish common management principles for sinonasal sarcomas. Methods This international consensus followed a modified Delphi method in seven steps, including statements definition by the core group, expert panel recruitment, and a two‐round survey. Sixty‐two statements on sinonasal sarcoma management were developed. Experts from multiple continents participated, and results were anonymized and analyzed between March and May 2025. Results A total of 44 invited experts were recruited, 43.2% otorhinolaryngologists/head and neck surgeons, 31.8% medical oncologists, and 25% radiation oncologists. Participants varied in age and experience, representing Europe (70.5%), North America (18.2%), South America (6.8%), and Asia (4.5%). Among all histologies, biphenotypic sarcoma, chondrosarcoma, leiomyosarcoma, and myofibrosarcoma are principally treated with an upfront surgical management, differently from Ewing sarcoma and rhabdomyosarcoma in which chemotherapy, eventually associated with radiotherapy, is often chosen. In the remaining histologies (angiosarcoma, liposarcoma, malignant peripheral nerve sheath tumor [MPNST], osteosarcoma, and synovial sarcoma), a precise multimodal treatment is less standardized and needs to be discussed on a case‐by‐case basis. Conclusion Sinonasal sarcomas require a histology‐driven approach to determine upfront treatment, whether surgical, medical, or multimodal. Despite this structured strategy, prognosis remains highly variable across subtypes. Multidisciplinary evaluation and individualized management in referral centers are crucial to address the biological diversity and anatomical complexity of these rare malignancies.

Background Global efforts to raise delirium awareness have been made over the past years, such as the formation of the iDelirium group and the institution, in 2017, of the annual World Delirium Awareness Day (WDAD) in March. In 2023, our group and researchers from around the world conducted a global one-day point prevalence study of delirium on WDAD. These strategies appear to improve delirium recognition and management. Objective To assess participants’ perceived impact of participating in the WDAD 2023 one-day point prevalence study and to gather feedback on the survey process to inform future campaigns. Methods An online survey was administered to multiple national and clinical collaborators from 44 countries participating in the one-day global point delirium prevalence study on WDAD 2023. Using SurveyMonkey®, the survey was distributed via a snowball system, with participants’ consent implied through their involvement. The survey, developed iteratively to balance time and detail, consisted of six core questions, including closed and open formats. Data were collected from September 9th to October 9th, 2023, and qualitative and quantitative analyses were performed using Excel®. Quantitative data underwent statistical analysis using IBM® SPSS Statistics28. Results 49 out of 53 (93.45%) healthcare professionals responded to the survey: 71.43% reported increased awareness, and responses were almost equally divided between those who initiated projects (46.94%) and those who did not (53.06%). Most participants (93.88%) did not find the WDAD 2023 one-day point prevalence study in March burdensome, and all expressed interest in future participation. The WDAD 2023 one-day point prevalence study highlighted diverse projects, primarily focused on delirium awareness and education. The survey found suggestions for future improvements emphasizing more efficient, digital, and engaging research methods and a clear need for educational resources, particularly in ICU delirium. Conclusions Our survey finds that participation in WDAD 2023 one-day point prevalence study boosted delirium visibility, leading to ongoing awareness, interest in future studies, and practice changes that benefit patients and the healthcare system. Further evidence-based research is needed to assess the impact of these campaigns on delirium recognition and management.

Abstract Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity. Methods Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests. Results In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC. Conclusions Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

Objectives: There is a paucity of research comparing the outcomes of medial ulnar collateral ligament (MUCL) repair with internal bracing to isolated MUCL reconstruction in professional baseball players. Further, the practice of supplementing a MUCL reconstruction with an internal brace, a "hybrid" reconstruction, has increased in the surgical treatment of MUCL injuries for professional baseball players, without any currently known published research defining the clinical outcomes of this modification. We sought to investigate the trends and outcomes of MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing. Using a matched cohort analysis, we also sought to compare the clinical outcomes of both MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing to isolated MUCL reconstructions, without internal bracing, in professional baseball players. Methods: The MLB Health and Injury Tracking System was used to identify all professional baseball players who underwent MUCL surgery, regardless of surgery technique, from 2010 to 2023. Professional players of all levels (MLB and MiLB) and players of all positions were included. Player demographics, injury characteristics, surgical details, and postoperative outcomes were obtained. Player demographics included age at surgery, position of play, professional level of play and surgical technique. Outcomes assessed were return to play (RTP) status, time to RTP, return to same level of play (RTSL), time to RTSL, revision MUCL surgery, and time to revision MUCL surgery, with a minimum of 2 years of follow up. Players were considered to have RTP if they participated in at least one game at any professional level. RTSL was defined as returning to the same league of professional play or higher. Patients undergoing MUCL repair and "hybrid" MUCL reconstruction with internal bracing were independently compared to propensity matched patients undergoing isolated MUCL reconstruction, without internal bracing, to assess for a difference in postoperative outcomes. Four subgroup analyses were conducted by further categorizing patients to MLB players, MiLB players, pitchers, and position players. Results: 76 patients underwent MUCL repair with internal bracing from 2016-2021 and were successfully propensity matched to 76 patients undergoing isolated MUCL reconstructions. Baseline patient demographic variables of MUCL repairs were statistically similar to those of controls except for age at time of surgery (24.5 vs 21.8; p<0.001). 81 patients underwent "hybrid" MUCL reconstructions with internal bracing from 2016-2021 and were successfully propensity matched to 81 patients undergoing isolated MUCL reconstructions. Baseline demographic variables of "hybrid" MUCL reconstructions were statistically similar to those of controls except for age at time of surgery (24.3 vs. 23.3; p=0.006). Compared to isolated MUCL reconstruction controls, all patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.2 vs. 546.2 days; p<0.001), shorter time to RTSL (mean 436.2 vs. 558.8 days; p<0.001), and shorter time to revision (mean 465.2 vs.1648 days; p=0.036). The number of patients who RTP at any level, RTSL, and number of revision surgeries were not significantly different. Compared to isolated MUCL reconstruction controls, all patients undergoing "hybrid" MUCL reconstructions demonstrated no significant differences with respect to the number of patients who RTP, time to RTP, number of patients who RTSL, days to RTSL, number of revision surgeries, and time to revision surgery. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 282.8 vs 507.3 days; p=0.008) and shorter time to RTSL (mean 299.7 vs. 598.0 days; p = 0.024). No other outcomes were significant. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 436.2 vs. 525.3 days; p=0.026). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 444.3 vs 550.7 days; p<0.001) and shorter time to RTSL (mean 451.7 vs. 556.5 days; p<0.001). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated no significant differences in outcomes. In evaluating pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.7 vs. 578.6 days; p<0.001), shorter time to RTSL (mean 434.8 vs. 591.6 days; p <0.001), and shorter time to revision surgery (mean 465.2 vs.1648 days; p=0.036). No other outcomes were significant. In pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 488.1 vs. 549.0 days; p=0.013) and shorter time to RTSL (mean 505.7 days vs. 577.0 days, respectively; p=0.021). No other outcomes were significant. Notably, all revision surgeries in occurred in pitchers only. Conclusions: Based on a matched cohort anaylsis of professional baseball players undergoing MUCL surgery, when compared to an isolated MUCL reconstruction, MUCL repair with internal bracing may allow for a shorter time to RTP and RTSL, with a shorter time to revision surgery. For pitchers, "hybrid" MUCL reconstruction may allow for a shorter time to RTP and RTSL. For MLB players, "hybrid" MUCL reconstruction may allow for a shorter RTP.

Objectives: The number of medial ulnar collateral ligament (MUCL) reconstructions are increasing. The epidemiology surrounding revision MUCL reconstructions in professional baseball players has not been well defined. The purpose of this study was to report the epidemiology of revision MUCL reconstruction in professional baseball players. The authors hypothesized that the number of revision MUCL reconstructions would increase over time and that the return to sport rate at the same level of play would be less than 70%. Methods: All professional baseball pitchers who underwent revision MUCL reconstruction between 2010-2023 were identified using the MLB Health and Injury Tracking System (HITS). Rate of return and time to return to play (RTP) and return to same level of play (RTSL) was recorded and analyzed for pitchers with a minimum follow up of 2 years. Surgical variables including technique and graft choice were also recorded. Results: Overall, 191 pitchers (avg age 26.0 years), underwent revision MUCL reconstruction. The average time between primary and revision surgery was 1,381 days (45 months). 130 (68%) of these players were MLB pitchers and the other 61 (32%) were MiLB pitchers. 59% of pitchers were able to RTSL at an average of 604 ± 250 days after surgery. 2023 was the year with most revision MUCL reconstructions (n = 27) and the fewest reconstructions were performed in 2010 and 2011 (n = 4). Monthly distribution demonstrates the highest surgery months to be May (17%), June (20%), and July (17%). Hamstring tendon autograft was found to be the most commonly used graft source (n = 90, 47%), compared to palmaris longus autograft (n = 67, 35%). No significant differences were found in the types of grafts used over time ( P = .238 for palmaris and P = .133 for hamstring). In terms of tunnel configuration, both the Modified Jobe and Docking techniques were used in equal occurrence (n = 70, 37%) Conclusions: Following revision MUCL reconstruction, only 72% of professional baseball pitchers were able to return to play at any level at an average of 556 days (18 months), and only 59% were able to return to the same level of play at an average of 604 days (20 months). The average time between primary and revision MUCL reconstruction was 45 months (3.75 years). Pitchers should be counseled on the relatively low RTSL rate and the prolonged time to RTSL.